Biodegradable polymer systems

ABSTRACT

The rate of degradation of polymers and polymer blends containing (poly) lactic acid can be increased and controlled by the inclusion of up to 10% (typically less than 1%) by weight of specific additives such as lauric acid or a derivative thereof such as the anhydride.

[0001] This invention relates to biodegradable polymeric materials,particularly to bioresorbable materials and to artifacts made therefrom.

[0002] Poly (lactic acid), also commonly known as PLA has been widelyused, either as the D-isomer or the mixed DL-form, for the manufactureof implant materials where bioresorbabilty is a required property.Although PLA is biodegradable it will normally take from 3 to 5 years tobe fully resorbed. A further disadvantage is that although it takes 3 to5 years to fully degrade the mechanical strength of implants made frompoly (L-lactic acid) (PLLA) will be lost within a fifth of that time Thein vivo degradation of PLA takes place predominately via anautocatalysed hydrolytic scission of the ester groups in the polymerchain according to the reaction:

[0003] Attempts to increase the carboxylic acid functionality of thepolymeric material and, hence, increase the rate of degradation of PLAhave been reported in the literature (“Modification of the rates ofchain cleavage of poly (ε-caprolactone) and related polyesters in thesolid state”, Journal of Controlled Release, 4, (1987) pp283-292.) inwhich samples of PLA have been contacted with carboxyl group-containingmaterials such as oleic acid. No effect on the rate of degradation wasreported. The effect of lactic acid monomer in PLA has also beeninvestigated and reported (“Effects of residual monomer on thedegradation of DL-lactide polymer” Hyon, Jamshidi & Ikada, PolymerInternational, 46 (1998), pp196-202). However, it was found that theadded monomer rapidly leached out of the polymer. Polymer blendscontaining 15 weight percent lactic acid exhibited a total weight lossof about 15% within the first week of a 10 week study and very littlefurther loss in the remaining weeks.

[0004] In U.S. Pat. No. 5,527,337 there is disclosed a biodegradeablestent formed from lactide polymers wherein, inter alia, an excipientsuch as ctric acid or fumaric acid can be incorporated during thepolymer processing. Other additives which which can be used toaccelerate stent degradation which are not acids themselves are alsodisclosed including the tertiary butyl ester of lauric acid and theditertiary butyl ester of fumaric acid.

[0005] U.S. Pat. No. 6,248,430 describes a laminate, for use in themanufacture of molded products for agricultural or civil engineeringpurposes. The laminate consists of a base layer comprising a lacticacid-based polymer having a degradation accelerator incorporated thereinand a barrier layer which comprises a lactic acid based polymer having alactide content of not more than 0.1% by weight, for the purpose ofpreventing the accelerator from leaking from the base polymer. Thelactic acid-based polymer comprises a polyester made of polylactic acidcomponent, lactic acid component dicarboxylic acid component, diolcomponent and/or polyether component or a mixture thereof. Examples ofmaterials useful as an accelerator include organic acids such as lactic,glyceric, tartaric, citric, lauric, stearic, oleic, succinic, adipicsebacic, benzoic and phthalic acids. The disclosure shows that theaccelerators are incorporated during the polymer forming process.

[0006] Although it is known in the prior art to attempt to increase thecarboxyl functionality by using acid based accelerators it has been aproblem to retain such accelerators within the polymer mass for asufficient period of time to allow control of the rate of degradation.The prior attempts to control degradation require either the use ofphysical barrier layers to retain the accelerator or the use of complexpolymer systems.

[0007] We have now found that it is possible to control the rate ofdegradation of lactic acid polymers by homogeously blending certainadditives which are both fully miscible with PLA and will not leach out.The blending process is simple and results in stable polymer blendswhich can be readily thermoformed, such as by injection molding to formimplantable medical devices which will both maintain their physicalstrength yet biodegrade in a predictable manner.

[0008] Thus in accordance with the present invention there is providedan implantable, biodegradable medical device formed from a homogeneouspolymer blend comprising a poly lactic acid in admixture, in an amountof not more than 10% by weight of the polymer blend, with an additivewhich is an acid or a derivative thereof selected from the groupconsisting of hexanoic acid, octanoic acid, decanoic acid, lauric acid,myristic acid, crotonic acid, 4-pentenoic acid, 2-hexenoic acid,undecylenic acid, petroselenic acid, oleic acid, erucic acid,2,4-hexadienoic acid, linoleic acid, linolenic acid, benzoic acid,hydrocinnamic acid, 4-isopropylbenzoic acid, ibuprofen, ricinoleic acid,adipic acid, suberic acid, phthalic acid, 2-bromolauric acid,2,4-hydroxydodecanoic acid, monobutyrin, 2-hexyldecanoic acid,2-butyloctanoic acid, 2-ethylhexanoic acid, 2-methylvaleric acid,3-methylvaleric acid, 4-methylvaleric acid, 2-ethylbutyric acid,trans-beta-hydromuconic acid, isovaleric anhydride, hexanoic anhydride,decanoic anhydride, lauric anhydride, myristic anhydride, 4-pentenoicanhydride, oleic anhydride, linoleic anhydride, benzoic anhydride,poly(azelaic anhydride), 2-octen-1-yl succinic anhydride and phthalicanhydride.

[0009] The additive concentration is chosen such that it must be fullymiscible with the polymer blend and should not leach out of the polymer.

[0010] As used herein the term “fully miscible” means that when an 0.5mm thick sheet of the polymer blend is visually inspected the sheet iseither uniformly transparent or, if the sheet is opaque, the opacity isuniform.

[0011] As used herein the term “not leach out of the polymer” is definedsuch that when a thin (thickness <1 mm) sample is immersed in an excessof PBS (Phosphate buffer solution), at least half of the added additiveremains in the sample after 1 week.

[0012] Aptly the polymer blend will contain not more than 5%, morepreferably not more than 2%, by weight of the additive and typically theblend will contain not more than 1% by weight of the additive. Preferredblends will contain not more than 2%, more preferably not more than 1%,by weight of the blend of lauric acid or a derivative thereof.

[0013] The amount of the additive chosen will also depend upon the rateof degradation desired. In vivo degradation occurs firstly by hydrolyticscission of the ester groups resulting in the formation of units ofincreasingly smaller molecular weight until only substantially lacticacid monomer remains. Thereafter, the lactic acid is metabolized andabsorbed into the body. It is only in the last stages of degradationthat mass loss occurs.

[0014] The mechanical properties of the implant are retained in theearly stages of degradation, even though the molecular weight maydecrease markedly. Eventually a critical molecular weight is reached andthe implant will cease to have any useful mechanical strength yet willnot have degraded sufficiently for resorption to occur.

[0015] We have found that a preferred additive for use in the inventionis lauric acid. This may be employed as the acid per se or, if desired,as a derivative, for example as the anhydride.

[0016] By the use of the blends for the present invention not only maythe total rate of degradation and resorption be controlled but it ispossible to control the rate of degradation in order to optimize themechanical properties. In many, surgical procedures, where the implantis required to provide temporary support until the condition has beentreated by the body's own natural repair or rebuilding activity. Whenthe support provided by the implant is no longer required it is oftendesirable that the strength of the implant be markedly reduced.

[0017] Thus in accordance with a further embodiment of the presentinvention there is provided an implantable, biodegradable medical devicehaving predetermined strength retention comprising a homogeneous blendof a polylactic acid in admixture with an additive as hereinabovedefined, in an amount, calculated as weight percent, based on the weightof the total polymer blend represented by the following equation:${\% \quad {additive}} = {M_{n\quad A}*100*\left\{ {\left\lbrack \frac{{L\quad {n\left( \frac{M_{n0}}{M_{n\quad s}} \right)}} - {t\quad k_{1}}}{t\quad k_{2}} \right\rbrack^{2} - \frac{1}{M_{n\quad 0}}} \right\}}$

[0018] where:—

[0019] M_(n0)=polymer initial molecular weight

[0020] M_(ns)=Mn at which the polymer looses strength

[0021] M_(nA)=molecular weight of the acid

[0022] t=Duration (weeks) that strength retention is required

[0023] k₁=constant 1

[0024] k₂=constant 2

[0025] The constants k₁ and k₂ are the slope and intercept of a graph ofthe degradation rate of a blend against the square root of the totalnumber of COOH groups in the blend. The degradation rate of a blend isthe slope of a graph of Ln(Mn) against degradation time in weeks.

[0026] The degradation rates of the additives employed as 2% by weightcomponent in a polylactic acid blend in the present invention are shownin the following table: Additive Degradation rate Hexanoic acid −0.0565Octanoic acid −0.0448 Decanoic acid −0.0472 Lauric acid −0.0326 Myristicacid −0.0281 Crotonic acid −0.0489 4-Pentenoic acid −0.0567 2-Hexenoicacid −0.0713 Undecylenic acid −0.07 Petroselenic acid −0.0542 Oleic acid−0.0442 Erucic acid −0.0315 2,4-Hexadienoic acid −0.0618 Linoleic acid−0.0488 Linolenic acid −0.0589 Benzoic acid −0.0798 Hydrocinnamic acid−0.0737 4-Isopropylbenzoic acid −0.0728 Ibuprofen −0.051 Ricinoleic acid−0.061 Adipic acid −0.0373 Suberic acid −0.0311 Phthalic acid −0.08552-Bromolauric acid −0.0769 2,4-Hydroxydodecanoic acid −0.0318Monobutyrin −0.0347 2-Hexyldecanoic acid −0.0339 2-Butyloctanoic acid−0.0467 2-Ethylhexanoic acid −0.0473 2-Methylvaleric acid −0.04113-Methylvaleric acid −0.0587 4-Methylvaleric acid −0.0553 2-Ethylbutyricacid −0.053 Trans-beta-hydromuconic acid −0.039 Isovaleric anhydride−0.0628 Hexanoic anhydride −0.0919 Decanoic anhydride −0.0807 Lauricanhydride −0.0698 Myristic anhydride −0.0626 4-Pentenoic anhydride−0.0888 Oleic anhydride −0.0504 Linoleic anhydride −0.0696 Benzoicanhydride −0.0817 Poly(azelaic anhydride) −0.0784 2-Octen-1-yl succinicanhydride −0.1012 Phthalic anhydride −0.0841

[0027] A further embodiment of the present invention provides theprovision of an additive which not only will control the rate ofdegradation but will delay the onset of the degradation process. Thisdelay may be achieved, aptly by the use of additives which areconvertible to the acidic form of the additive. Suitable derivatives areacid anhydrides which will, in an in vivo environment hydrolyse to thecorresponding acid. Preferred anhydrides include lauric anhydride andbenzoic anhydride, in amounts of, aptly, not more than 5%, more aptly,not more than 2% and, typically, not more than 1% by weight of thepolymer blend.

[0028] Thus specifically the present invention provides an implantable,biodegradable medical device having predetermined strength retentioncomprising a homogeneous blend of a polylactic acid in admixture withlauric anhydride or benzoic anhydride in an amount, calculated as weightpercent, based on the weight of the total polymer blend, represented bythe following equation:${\% \quad {additive}} = {M_{n\quad A}*100*\left\{ {\left\lbrack \frac{{L\quad {n\left( \frac{M_{n0}}{M_{n\quad s}} \right)}} - {t\quad k_{1}}}{t\quad k_{2}} \right\rbrack^{2} - \frac{1}{M_{n\quad 0}}} \right\}}$

[0029] where M_(n0), M_(ns), M_(nA), k₁ and k₂ are as defined herein andt is the duration (weeks) that strength retention is required once onsetof degradation has comenced

[0030] The polymeric component of the polymer blends useful for theinvention essentially comprise a poly lactic acid. The poly lactic acidmay be present as a homopolymer or as a co-polymer, for example aco-polymer of lactic acid and glycolic acid (known as PLA/PGAco-polymer). The polymer blend may also contain other polymericcomponents blended therewith. Thus the blend may, in addition to theadditive, consist of a blend of polylactic acid, PLA/PGA co-polymer.Other examples of suitable blend include blends of PLA or PLA/PGAco-polymer either alone or in admixture with each other, together withhydroxy apatite.

[0031] The polymer blends used for the present invention may be producedby known processes such as solution blending wherein the additive isblended directly into a solution of a polymeric component comprising PLAin, for example, chloroform. The solution blend is then dried.

[0032] The thus formed solid blend may then be formed per se into themedical device of the invention, by known processes such as compressionmoulding or extrusion or into components, such as fibres which may befurther processed to form devices in accordance with the presentinvention.

[0033] Alternatively, the blends may be further blended or ortherwiseformulated with other materials to form medical devices in accordancewith the invention. Thus the additive-containing blends may be utilizedas the matrix component of a composite material which is then fabricatedinto a biodegradable medical device.

[0034] The medical devices of the invention are biodegradable and anyimplantable devices where temporary residence only is required. Examplesof such devices include sutures, suture anchors, soft tissue anchors,interference screws, tissue engineering scaffolds, maxillo-facialplates, fracture fixation plates and rods.

[0035] The polymer blends themselves are believed to be novelcompositions of matter.

[0036] Accordingly, the present invention further provides a polymerblend, useful for the manufacture of biodegradable medical devicescomprising polylactic acid in admixture with an additive in an amount ofnot more than 10% by weight of the blend of at least one of hexanoicacid, octanoic acid, decanoic acid, lauric acid, myristic acid, crotonicacid, 4-pentenoic acid, 2-hexenoic acid, undecylenic acid, petroselenicacid, oleic acid, erucic acid, 2,4-hexadienoic acid, linoleic acid,linolenic acid, benzoic acid, hydrocinnamic acid, 4-isopropylbenzoicacid, ibuprofen, ricinoleic acid, adipic acid, suberic acid, phthalicacid, 2-bromolauric acid, 2,4-hydroxydodecanoic acid, monobutyrin,2-hexyldecanoic acid, 2-butyloctanoic acid, 2-ethylhexanoic acid,2-methylvaleric acid, 3 -methylvaleric acid, 4-methylvaleric acid,2-ethylbutyric acid, trans-beta-hydromuconic acid, isovaleric anhydride,hexanoic anhydride, decanoic anhydride, lauric anhydride, myristicanhydride, 4-pentenoic anhydride, oleic anhydride, linoleic anhydride,benzoic anhydride, poly(azelaic anhydride), 2-octen-1-yl succinicanhydride or phthalic anhydride.

[0037] Aptly the blend will comprise not more than 5% by weight of theadditive and preferably no more than 2% by weight of the additive.

[0038] The present invention will be illustrated by reference to thefollowing and accompanying drawings.

EXAMPLE 1

[0039] Blends of poly(L-lactic acid) containing lauric acid, in amountsrespectively, 2% and 5% by weight of the blend, were prepared by firstdry blending the solid materials and then solution blending thematerials by roller mixing the solid mixture (10% by weight) withchloroform (90% by weight). After complete dissolution of the solids,the solutions were cast onto an open tray, left to dry (in a fumecupboard) at ambient temperature for 24 hours and dried for a further 24hours under vacuum at ambient temperature. A control sample was alsoprepared by solution blending poly(L-lactic acid) alone with chloroformand drying the cast solution under the same conditions as the lauricacid-containing samples.

[0040] The dried cast films were then comminuted and approximately 10 gmcharges of the blends were compression moulded between two sheets ofmould release sheets maintained 0.5 mm apart. The charges were warmedfor 5 minutes prior to moulding and fed into the mould at a temperatureof 195° C. pressure of 100N over a period of 90 seconds to form sheets.The resultant sheets were observed to be transparent.

[0041] The sheets were cut into strips and subjected to simulateddegradation by immersion in standard phosphate buffer solution (PBS),maintained at 37° C. for 10 weeks.

[0042] During the ten week test period samples were analysed:

[0043] to determine molecular weight of the polymer blend (to measurethe degree of degradation),

[0044] to determine the lauric acid in the polymer (to measure thedegree of leaching of the lauric acid additive),

[0045] to determine the amount of Lactic acid in the PBS (to measure theamount of degradation products released into the PBS buffer).

[0046] The decrease in molecular weight is reported in FIG. 1. Thelauric acid remaining in the sample was determined by GC-MS. Sampleswere weighed (˜50 mg) and 2 ml chloroform added. These were sonicateduntil the polymer dissolved. 20 ml of diethyl ether was added toprecipitate out the polymer, this was transferred to a 50 ml volumetricand made to the mark with diethyl ether. An aliquot of the samples wasvialled for analysis by GC-MS. The results for samples at weeks 0 and 10are shown in FIG. 2.

[0047] Samples of the PBS were also analysed by HPLC to determine theamount of lactic acid (to measure resorption potential). 31 ml aliquotsof the PBS were taken at each time interval and analysed under thefollowing conditions: Mobile Phase: 0.005N H₂SO₄ in water Column: Rezex8μ 8% H. Organic Acids - 300 × 7.80 mm Flow Rate: 0.6 ml/min InjectionVolume: 100 μl Column 63° C. Temperature: Wavelength: 210 nm Runtime 20min

[0048] The lactic acid content of the PBS is shown in FIG. 3.

EXAMPLE 2

[0049] Blends of poly(DL-lactic acid) containing lauric acid, in amountsrespectively, 2% and 4% by weight of the blend, were prepared using themethod described for Example 1.

[0050] The sheets were cut into strips and subjected to simulateddegradation by immersion in standard phosphate buffer solution (PBS),maintained at 37° C. for 8 weeks.

[0051] During the eight week test period samples were analysed:

[0052] to determine molecular weight of the polymer blend (to measurethe degree of degradation),

[0053] Lactic acid (to measure the amount of degradation productsreleased into the PBS buffer).

[0054] The decrease in molecular weight is reported in FIG. 4, thelactic acid released into the PBS buffer in FIG. 5.

EXAMPLE 3

[0055] A blend of poly(L-lactic acid) containing 5% lauric acid wasprepared by first dry blending the solid materials and then solutionblending the materials by roller mixing the solid mixture (10% byweight) with chloroform (90% by weight). After complete dissolution ofthe solids, the solutions were cast onto an open tray, left to dry (in afume cupboard) at ambient temperature for 24 hours and dried for afurther 24 hours under vacuum at ambient temperature. A control samplewas also prepared by solution blending poly(L-lactic acid) alone withchloroform and drying the cast solution under the same conditions as thelauric acid-containing samples.

[0056] The dried cast films were then comminuted and extruded at 180° C.to produce rods with a diameter of approx 2 mm. The resultant rods wereobserved to be slightly opaque, but uniform in colour.

[0057] The rods were then subjected to simulated degradation byimmersion in standard phosphate buffer solution (PBS), maintained at 37°C. for 8 weeks.

[0058] During the eight week test period samples of the billets wereanalysed:

[0059] to determine molecular weight of the polymer blend (to measurethe degree of degradation),

[0060] to determine the tensile strength of the rods.

[0061] The decrease in molecular weight is reported in FIG. 6. Thetensile strength of the rods was measured using a gauge length of 40 mmand a test speed of 10 mm/min, the results are reported in FIG. 7.

EXAMPLE 4

[0062] A blend of poly(L-lactic acid) containing 1% lauric acid wasprepared by first dry blending the solid materials and then extrudingthe mixture at 195° C. The subsequent polymer blend was then analysed todetermine the lauric acid content, which was measured at 0.9%. Theresultant rod material was observed to be transparent.

EXAMPLE 5

[0063] Blends of poly(L-lactic acid) containing lauric anhydride, inamounts respectively, 2% and 5% by weight of the blend, were prepared byfirst dry blending the solid materials and then solution blending thematerials by roller mixing the solid mixture (10% by weight) withchloroform (90% by weight). After complete dissolution of the solids,the solutions were cast onto an open tray, left to dry (in a fumecupboard) at ambient temperature for 24 hours and dried for a further 24hours under vacuum at ambient temperature. A control sample was alsoprepared by solution blending poly(L-lactic acid) alone with chloroformand drying the cast solution under the same conditions as the lauricacid-containing samples.

[0064] The dried cast films were then comminuted and approximately 10 gmcharges of the blends were compression moulded between two sheets ofmould release sheets maintained 0.5 mm apart. The charges were warmedfor 5 minutes prior to moulding and fed into the mould at a temperatureof 195° C., pressure of 100N over a period of 90 seconds to form sheets.The resultant sheets were observed to be transparent.

[0065] The sheets were cut into strips and subjected to simulateddegradation by immersion in standard phosphate buffer solution (PBS),maintained at 37° C. for 8 weeks.

[0066] During the eight week test period samples of the sheets wereanalysed to determine molecular weight of the polymer blend (to measurethe degree of degradation). The decrease in molecular weight is reportedin FIG. 8.

EXAMPLE 6

[0067] The process of Example 5 was repeated using a blend of poly(L-lactic acid) containing 2% by weight benzoic acid anhydride. Thereduction of molecular weight with time is shown in FIG. 9.

[0068] The decrease in molecular weight over the twenty week test periodshowed that there was very little degradation (loss in molecular weight)within the first ten weeks

EXAMPLE 7

[0069] The process of Example 1 was repeated to make blends of poly(L-lactic acid) containing 2% by weight of the following acids:

[0070] Phthalic acid

[0071] 2-Hexanoic

[0072] 4-Isopropylbenzoic acid

[0073] Hydrocinnamic acid

[0074] 2-Bromolauric acid

[0075] Benzoic acid

[0076] Lauric acid

[0077] Undecylenic acid

[0078] 2-4 Hexadienoic

[0079] PLA control

[0080] The results of a plot of molecular weight decreas with time isshown in FIG. 10.

EXAMPLE 8

[0081] The product of Example 4, ie rods of a blend of poly (L-lacticacid) containing 0.9% by weight of Lauric acid, were cut up into shortlengths (typically about 3 mm). This material was then formed into aninterference screw (for soft tissue anchorage) by injection mouldingusing an Arburg 270M All Rounder 500-90 machine with the followingconditions:

[0082] Temp at nozzle=224° C.

[0083] Barrel Temp=235° C.

[0084] Injection pressure=1500 bar

[0085] Mould temp=18° C.

[0086] The resultant moulded devices had filled the mould well and weretransparent.

1. An implantable, biodegradable medical device formed from ahomogeneous polymer blend comprising a lactic acid polymer in admixture,in an amount of not more than 10% by weight of the polymer blend, withan additive which is an acid or a derivative thereof selected from thegroup consisting of hexanoic acid, octanoic acid, decanoic acid, lauricacid, myristic acid, crotonic acid, 4-pentenoic acid, 2-hexenoic acid,undecylenic acid, petroselenic acid, oleic acid, erucic acid,2,4-hexadienoic acid, linoleic acid, linolenic acid, benzoic acid,hydrocinnamic acid, 4-isopropylbenzoic acid, ibuprofen, ricinoleic acid,adipic acid, suberic acid, phthalic acid, 2-bromolauric acid,2,4-hydroxydodecanoic acid, monobutyrin, 2-hexyldecanoic acid,2-butyloctanoic acid, 2-ethylhexanoic acid, 2-methylvaleric acid,3-methylvaleric acid, 4-methylvaleric acid, 2-ethylbutyric acid,trans-beta-hydromuconic acid, isovaleric anhydride, hexanoic anhydride,decanoic anhydride, lauric anhydride, myristic anhydride, 4-pentenoicanhydride, oleic anhydride, linoleic anhydride, benzoic anhydridge,poly(azelaic anhydride), 2-octen-1-yl succinic anhydride and phthalicanhydride.
 2. An implantable, biodegradable medical device havingpredetermined strength retention comprising a homogeneous blend of alactic acid polymer in admixture with an additive as hereinabovedefined, in an amount, calculated as weight percent, based on the weightof the total polymer blend represented by the following equation:${\% \quad {additive}} = {M_{n\quad A}*100*\left\{ {\left\lbrack \frac{{L\quad {n\left( \frac{M_{n0}}{M_{n\quad s}} \right)}} - {t\quad k_{1}}}{t\quad k_{2}} \right\rbrack^{2} - \frac{1}{M_{n\quad 0}}} \right\}}$

Where: M_(n0)=polymer initial molecular weight M_(ns)=Mn at which thepolymer loses strength M_(nA)=molecular weight of the acid T—Duration(weeks) that strength retention is required once the onset ofdegradation has commerced K₁=constant 1 K₂=constant 2
 3. A device asclaimed in claim 1 wherein the additive is lauric acid anhydride orbenzoic acid anhydride.
 4. A device as claimed in claim 1 wherein thepolymer blend contains not more than 2%, by weight of the additive.
 5. Adevice as claimed in claim 1 wherein the lactic acid polymer is polylactic acid.
 6. A device as claimed in claim 1 wherein the lactic acidpolymer is a copolymer with glycolic acid.
 7. A device as claimed inclaim 1 wherein the polymer blend comprises additional polymericcompounds.
 8. A device as claimed in claim 1 wherein the polymer blendis the matrix component of a composite material from which the device isformed.
 9. A device as claimed in claim 1 in the form of a suture,suture anchor, soft tissue anchor, interference screw, tissueengineering scaffold, maxial-facial plate, or a fracture fixation plateor rod.
 10. A polymer blend, useful for the manufacture of biodegradablemedical devices comprising polylactic acid in admixture with an additivein an amount of not more than 10% by weight of the blend of at least oneof hexanoic acid, octanoic acid, decanoic acid, lauric acid, myristicacid, crotonic acid, 4-pentenoic acid, 2-hexenoic acid, undecylenicacid, petroselenic acid, oleic acid, erucic acid, 2,4-hexadienoic acid,linoleic acid, linolenic acid, benzoic acid, hydrocinnamic acid,4-isopropylbenzoic acid, ibuprofen, ricinoleic acid, adipic acid,suberic acid, phthalic acid, 2-bromolauric acid, 2,4-hydroxydodecanoicacid, monobutyrin, 2-hexyldecanoic acid, 2-butyloctanoic acid,2-ehtylhexanoic acid, 2-methylvaleric acid, 3-methylvaleric acid,4-methylvaleric acid, 2-ethylbutyric acid, trans-beta-hydromuconic acid,isovaleric anhydride, hexanoic anhydride, decanoic anhydride, lauricanhydride, myristic anhydride, 4-pentenoic anhydride, oleic anhydride,linoleic anhydride, benzoic anhydride, poly(azelaic anhydride),2-octen-1-ylsuccinic anhydride or phthalic anhydride.
 11. A blend wasclaimed in claim 10 comprising not more than 5% by weight of theadditive.
 12. A blend was claimed in claim 11 comprising no more than 2%by weight of the additive.